Pig fetuses infected with Zika virus develop severe brain pathology

Gepubliceerd op

4 april 2018

Emerging Microbes & Infections (Nature publishing group) published a study of Wageningen Bioveterinary Research (WBVR) in which pregnant pigs were used to study Zika virus (ZIKV) pathogenesis. Pigs share many anatomical and physiological features with humans, so this species may be an attractive alternative human surrogate for ZIKV research. ZIKV is a mosquito-borne flavivirus that became associated with microcephaly in newborns and Guillain-Barré syndrome in adults after its emergence in the Pacific and the Americas in 2015.

Study design and results

WBVR inoculated 20 porcine fetuses in utero and assessed the effect of ZIKV on brain development 4 weeks later. All inoculated fetuses presented mild to severe neuropathology, characterized by a depletion of neurons in the cerebral cortex. In most cases, neuronal depletion was confined to specific cerebral lobes without affecting brain size, whereas in severe cases a more generalized depletion resulted in microcephaly.

ZIKV models

First insights into ZIKV-mediated neuropathology came from studies with mice. However, the major differences in the physiology, anatomy, and development of the rodent and human brain makes extrapolation of observations made in mouse experiments to humans not always appropriate. The application of mouse models to study the effect of ZIKV on brain development is further limited by the short gestation period of mice compared with humans. Nonhuman primates are considered the best human surrogates for studying human infectious diseases and have indeed proven extremely valuable in ZIKV research. However, the use of large numbers of non-human primates, particularly during gestation, is under severe societal scrutiny.

Implications

The presented fetal pig model can be used to study fundamental aspects of congenital ZIKV syndrome and may facilitate the evaluation of ZIKV therapeutics. The study also supports the notion that congenital ZIKV infection induces more than just microcephaly.